Dysregulated growth and invasion characterize oral squamous cell carcinoma (SCC). SCC invasion into adjacent tissue requires integrin- mediated cell migration through the underlying extracellular matrix. Before they actively invade, the carcinoma cells must initiate nascent attachments to the underlying extracellular matrix and disengage their extensive junctional adhesions. In contrast to normal mucosal epithelium, where proliferation is restricted to basal keratinocytes, suprabasal oral SCC cells have lost their requirement for anchorage to extracellular matrix and continue to proliferate uncontrollably in the absence of basement membrane adhesions. The long-term goal of the proposed research is to define the importance of adhesion in regulating invasion, survival and growth in oral SCC cells. In this proposal three specific aims will be addressed: 1) Identify specific integrin-ligand pairs that induce uncoupling of intercellular adhesion and stimulate cell motility. 2) Determine whether disruption of oral SCC cell adhesion will modulate anchorage-independent survival and growth. The experiments will utilize human oral SCC cell lines and the animal provided in Core B with histopathology to be performed in Core C. Extensive interactions related to integrin adhesion and cell growth are planned with Project. The proposed studies will establish whether specific receptor families generate compensatory signals that regulate motility, survival and growth. This information will help expand our understanding, at the molecular, of the role of adhesion in controlling unregulated invasion and intratumoral proliferation of oral cancer.